The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+-ATPases. Na+/K+-ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+-ATPase is encoded by multiple genes. This gene encodes an alpha 3 subunit. ATP1A3 is expressed early in human development, likely underlying pathophysiology related to several ATP1A3 related diseases.
Disease causing variants of the ATP1A3 gene are known to cause a variety of movement disorders and epilepsies. The known associations include a variety of syndromes, in approximate order of presentation:
- Malformation of Cortex Development, including polymicrogyria
- Developmental and epileptic encephalopathy
- Alternating hemiplegia of childhood (AHC)
- Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss (CAPOS/CAOS syndrome)
- Very early-onset schizophrenia
- Rapid onset dystonia-parkinsonism (RDP, also known as DYT12)
- Fever induced paroxysmal weakness and encephalopathy (FIPWE)
- Recurrent episodes of cerebellar ataxia (RECA)
In mice, mutations in this gene are associated with epilepsy. By manipulating this gene in the offspring of such mice, epilepsy can be avoided.